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Abstract While Coronavirus disease 2019 (COVID-19) vaccines have proven to be both effective and generally safe, rare but severe adverse events following immunization (AEFIs) are described. Autoantibodies to platelet factor-4 are associated with catastrophic thrombotic AEFIs, but comprehensive investigations of other autoantibodies are lacking. We aimed to detect and describe autoantibodies targeting coagulation-related proteins in a population-wide cohort (SWEDEGENE) including AEFIs attributed to COVID-19 vaccines in Sweden. Subjects were recruited from December 2020 to October 2022 and were stratified based on diagnosis and COVID-19 exposure. Screening was carried out in two phases, with a multiplex bead-based assay in the first subset (until September 2021) and with targeted assays for the second (until October 2022). Positivity was defined based on absolute, relative, and biological/technical thresholds. Patients with coagulation-related AEFIs were older and the Vaxzevria vaccine was overrepresented in this group. Two cases had antiphospholipid antibodies but none had PF4 antibodies. We identified six positives for protein S autoantibodies. Protein S concentrations were negatively correlated with autoantibody response in patients with immunoreactivity and functional analysis revealed low protein S activity in three subjects. Our population-wide analysis reveals cases with autoantibodies against protein S which possibly underlie coagulopathic AEFIs.

Abstract COVID-19 is a severe respiratory disease affecting millions worldwide, causing significant morbidity and mortality. Adrenomedullin (bio-ADM) is a vasoactive hormone regulating the endothelial barrier and has been associated with COVID-19 mortality and other adverse events. This prospective cohort pilot study included 119 consecutive patients with verified SARS-CoV-2 infection admitted to two intensive care units (ICUs) in Southern Sweden. Bio-ADM was retrospectively analysed from plasma on ICU admission, and days 2 and 7. Information on comorbidities, adverse events and mortality was collected. The primary outcome was 90-day mortality, and secondary outcomes were markers of disease severity. The association between bio-ADM and outcomes was analysed using survival analysis and logistic regression. Bio-ADM on admission, day 2, and day 7 only moderately predicted 90-day mortality in univariate and multivariate Cox regression. The relative change in bio-ADM between sample times predicted 90-day mortality better even when adjusting for the SAPS3 score, with an HR of 1.09 (95% CI 1.04–1.15) and a C-index of 0.82 (95% CI 0.72–0.92) for relative change between day 2 and day 7. Bio-ADM had a good prediction of the need for renal replacement therapy in multivariate Cox regression adjusting for creatinine, where day 2 bio-ADM had an HR of 3.18 (95% CI 1.21–8.36) and C-index of 0.91 (95% CI 0.87–0.96). Relative changes did not perform better, possibly due to a small sample size. Admission and day 2 bio-ADM was associated with early acute kidney injury (AKI). Bio-ADM on ICU admission, day 2 and day 7 predicted 90-day mortality and dialysis needs, highlighting bio-ADM’s importance in COVID-19 pathophysiology. Bio-ADM could be used to triage patients with a risk of adverse outcomes and as a potential target for clinical interventions.

Objective This study described the experiences and perceptions of how primary health care professionals (PHCPs) support patients with venous leg ulcers (VLUs) in self-care monitoring.Design A qualitative approach with reflexive thematic analysis was used, with 24 individual qualitative open interviews.Setting Primary health care clinics and community health care in four southern regions in Sweden.Subjects Registered nurses, district nurses and nurse assistants who had experience of caring for patients with VLUs. In total, 24 interviews were conducted with PHCPs in Sweden.Results PHCPs have a vital role in promoting patient independence and responsibility, identifying needs and adapting care strategies, while also recognising unmet needs in patients with VLUs.Conclusion PHCPs actively monitor patients’ self-care and establish caring relationships. They see a need for a structured primary health care work routine for ulcer management.

Abstract Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that is a disease-modifying drug candidate for Parkinson’s disease. CDNF has pleiotropic protective effects on stressed cells, but its mechanism of action remains incompletely understood. Here, we use state-of-the-art advanced structural techniques to resolve the structural basis of CDNF interaction with GRP78, the master regulator of the unfolded protein response (UPR) pathway. Subsequent binding studies confirm the obtained structural model of the complex, eventually revealing the interaction site of CDNF and GRP78. Finally, mutating the key residues of CDNF mediating its interaction with GRP78 not only results in impaired binding of CDNF but also abolishes the neuroprotective activity of CDNF-derived peptides in mesencephalic neuron cultures. These results suggest that the molecular interaction with GRP78 mediates the neuroprotective actions of CDNF and provide a structural basis for development of next generation CDNF-based therapeutic compounds against neurodegenerative diseases.

Abstract Introduction Patient education programmes focusing on risk factor modification and lifestyle changes are well established as part of cardiac rehabilitation in patients with coronary artery disease (CAD). As participation rates are low, digital patient education programmes (DPE) are interesting alternatives to increase access. Understanding patients’ perceptions of DPE are important in terms of successful implementation in clinical practice but are not well known. Therefore, the aim of this study was to assess patients’ perceptions of using a DPE in terms of end-user acceptance and usability, perceived significance for lifestyle changes and secondary preventive goal fulfilment in patients with CAD. Methods This was a cross-sectional survey-based study. The survey was distributed to all 1625 patients with acute coronary syndrome or chronic CAD with revascularisation, who were registered users of the DPE between 2020 and 2022 as part of cardiac rehabilitation. The survey contained 64 questions about e.g., acceptance and usability, perceived significance for making lifestyle changes and secondary preventive goal fulfilment. Patients who had never logged in to the DPE received questions about their reasons for not logging in. Data were analysed descriptively. Results A total of 366 patients (mean age: 69.1 ± 11.3 years, 20% female) completed the survey and among those 207 patients (57%) had used the DPE. Patients reported that the DPE was simple to use (80%) and improved access to healthcare (67–75%). A total of 69% of the patients were generally satisfied with the DPE, > 60% reported that the DPE increased their knowledge about secondary preventive treatment goals and approximately 60% reported having a healthy lifestyle today. On the other hand, 35% of the patients would have preferred a hospital-based education programme. Among the 159 patients (43%) who had never used the DPE, the most reported reason was a perceived need for more information about how to use the DPE (52%). Conclusions This study shows an overall high level of patient acceptance and usability of the DPE, which supports its continued development and long-term role in cardiac rehabilitation in patients with CAD. Future studies should assess associations between participation in the DPE and clinical outcomes, such as secondary preventive goal fulfilment and hospitalisation.

Manure application performed in autumn requires regulation due to the risk of nitrogen (N) leaching during winter. On the other hand, application of manure in spring can pose some practical problems depending on the risk for N immobilization and the difficulty in ploughing heavy clay soils during this time of year. The risk for leaching is likely to differ between different soil texture and manure characteristics. In this study, we sought to estimate the risk for nitrogen leaching depending on the carbon/nitrogen ratio (C/N) of the manure, time for manure application, and soil type. We combined 3-year lysimeter experiments with 2-year field plot experiments and laboratory soil incubations and compared results with those from an empirical model. We compared effects of manure application on two soils (silty clay and loamy sand) and solid manures with different representing C/N ratios. In incubations, only manure with a C/N-ratio below 14 contributed with significant amounts of leachable N during the first months after application. In the lysimeter study, N leaching was unaffected by the timing of the application of the manure with C/N-ratio 18. However, regarding manure with C/N-ratio 10, N leaching was elevated with 10–15 kg N per ha after manure application in October compared to November and March on both soil types. The mineral N analyses from soil profiles in the field experiments showed a similar pattern, however, the increase was higher on the loamy sand compared to the silty clay. The ammonia emissions did not differ between manure types, but were on average 24% of applied NH4-N after application in October when air temperature was on average 12°C compared to only 3% of applied NH4-N in November and March when air temperature was on average 5°C. Similar to lysimeter results, the modelled N leaching was higher the earlier the manure application occurred in autumn. However, the model also predicted increased leaching for the manure with a high C/N-ratio, and a smaller effect on leaching on clay soil. Considering this, the model calculations overestimated the leaching effects from manure with a high C/N-ratio and underestimated the leaching effects on clay soil.

ABSTRACT: Most commercial laying hens suffer from sternum (keel) bone damage including deviations and fractures. X-raying hens, followed by segmenting and assessing the keel bone, is a key to automating the monitoring of keel bone condition. The aim of the current work is to train a deep learning model to segment the keel bone out of whole-body x-ray images. We obtained full-body x-ray images of laying hens (n = 1,051) and manually drew the outline of the keel bone on each image. Using the annotated images, a U-net model was then trained to segment the keel bone. The proposed model was evaluated using 5-fold cross validation. We obtained high segmentation accuracy (Dice coefficients of 0.88–0.90) repeatably over several validation folds. In conclusion, automatic segmentation of the keel bone from full-body x-ray images is possible with good accuracy. Segmentation is a requirement for automated measurements of keel geometry and density, which can subsequently be connected to susceptibility to keel deviations and fractures.

Resilience comprises positive adaptation to stress and has been extensively studied in the context of breast cancer. Nevertheless, specific experiences of breast cancer survivors in relation to resilience are unknown. The aim of this study was to explore the diverse experiences of important resilience aspects in breast cancer survivors. We conducted semi-structured interviews with 25 breast cancer survivors residing in Sweden. We used thematic analysis to analyze the data. We identified three themes relevant for resilience, each containing several subthemes: “I will try to keep the spirits up”: Struggling with agency in the face of uncontrollability, “You know that you are not alone”: Social support and collective survivorship for better and for worse, and “I try to leave that behind me”: Conceptualizing cancer as a closed chapter or a constant. Thus, having agency in relation to one’s thoughts, feelings, treatment, health, and daily functioning, having support from others, and conceptualizing breast cancer as a closed chapter were interpreted as important aspects of resilience.

Keel bone damage, include deviations and fractures, is common in both white and brown laying hens, regardless of the housing system. Radiography for assessing birds’ keel bones is was proposed by previous studies. However, radiographs show only 2 out of 3 dimensions of the dissected keel bones. The current study aimed to (1) investigate the association of radiographic optical density (keel and tibiotarsal) and geometry (keel) with dissected keel bone pathology. Previous studies suggested that keel bone fractures may result from internal pressure exerted by pelvic cavity contents. The current study also aimed to (2) investigate the potential associations between pelvic dimensions and measures of keel bone damage. A sample of 200 laying hens on a commercial farm were radiographed at 16, 29, 42, 55, and 68 weeks, and culled at the end of the laying period (week 74). The birds were examined post-mortem for pelvic dimensions and underwent whole-body radiography, followed by keel and tibiotarsal bone dissection and radiography, and keel bone scoring. The radiographs were used to estimate radiographic optical density (keel and tibiotarsal bone) and keel bone geometry (ratio of keel bone length to mid-depth). The method for on-farm radiography of laying hens, including live bird restraint, positioning for live keel imaging, and post-imaging measurements, was developed, tested, and found to be reproducible. The radiographs (1,116 images of 168 birds) and the respective measurements and post-mortem scores of keel bones are also provided for further development of radiographic metrics relevant to keel bone damage. Some longitudinal radiographic measurements of keel geometry (ratio of length to mid-depth) and optical density (keel and tibiotarsal) showed associations with the damage (deviations/fractures) observed on the dissected keel bones. The associations of keel damage were clearer with the radiographic keel geometry than with keel and tibiotarsal optical density, also clearer for the keel deviations than for keel fractures. The higher radiography ratio of keel length to mid-depth at weeks 42, 55 and 68 of age, the larger deviations size observed on the dissected keels at age of 74 weeks. The higher the tibiotarsal radiographic optical density at week 55 of age, the lower deviations size and fractures count observed on the dissected keels at age of 74 weeks. Pelvic dimensions showed a positive correlation with body weight, but a larger pelvic cavity was associated with increased keel bone damage. These findings lay the foundations for future use of on-farm radiography in identifying appropriate phenotypes for genetic selection for keel bone health.

Lignin extracted from black liquor in chemical pulp mills can potentially replace fossil carbon feedstocks in fuels and materials, thereby increasing the economic and environmental added values of woody biomass. However, since lignin extraction reduces the electricity generation of the mill, the added value depends on the characteristics of the electricity market in which the mill operates. In this study, a model mill is exposed to two different electricity price profiles: the low and steady prices of south-central Sweden in Year 2019; and the high and volatile prices of the same region in Year 2022. For the model mill, investments in lignin extraction designed to increase pulp production are economically viable and have low levels of sensitivity to electricity price levels and price volatility. The viability of lignin extraction without increased pulp production depends on the relationship between the electricity and lignin prices. With stable electricity prices, or steady mill operation, a rule-of-thumb holds that for lignin extraction to be viable, the lignin price (€/t) must be 1.8-times the average electricity price (€/MWh) plus 40 €/t for the supply of chemicals. With volatile electricity prices and flexible operation of the recovery boiler, the mill can shift the loss in electricity sales to low-price hours, thereby saving 15–70 % of the operational costs of lignin extraction, as compared to steady operation. This effect can be further enhanced by increasing the capacity of the lignin extraction process or extending the size of the black liquor storage tank. The proposed flexibility measures allow the market-integrated pulp mill to export lignin to replace fossil carbon supplies in other sectors, while supporting the electricity system during hours with high demand and low supply.

Material flow analysis is an important tool for estimating material flows and embedded emissions of transport infrastructure. Missing attributes tend to be a major barrier to accurate estimates. In this study a machine learning model is developed to estimate the missing data in a statistics dataset of roads, to enable a bottom-up material stock and flow analysis. The proposed approach was applied to the Swedish road network to predict missing data for road width in the statistical dataset. The predicted hybrid dataset was then used to estimate material stocks, flows, and embodied emissions from Year 2020 to Year 2045 using decarbonization scenarios with a supply chain perspective. The study demonstrates that machine learning models can be used to enable national-level material stock and flow analyses of roads. Multiple machine learning algorithms were tested, and the best performing model achieved an R2 value of 0.784. In the scenario-based analysis, the embodied emissions of Swedish roads could be reduced by up to 51% using available materials.

Abstract Background Many adolescent males visit a general practitioner regularly, yet many report unmet health needs and negative experiences. This indicates a gap between provided healthcare and the needs of adolescent males. In order to improve adolescent males’ possibilities to discuss their health concerns with general practitioners, the study’s aim was to explore and describe how adolescent males understand and assign meaning to their experiences of consultations with general practitioners. Methods This qualitative study was conducted at two healthcare centres in mid-Sweden in 2022. Nine males 15 to 19 years old described their experiences in semi-structured interviews immediately after consulting a general practitioner, regardless of reason for the consultation and whether or not accompanied by a parent. The analysis was guided by thematic analysis according to Braun & Clarke and reflective lifeworld theory’s concepts of openness and sensitivity. Results One overarching theme, To be listened to, and three themes were developed: To handle insecurity and uneasiness, To be understood and cared for, and To get parental support on his terms. In a good appointment, the general practitioner cares about him, listens attentively, and takes him seriously. More importantly, the general practitioner’s understanding permeates the consultation, so that all aspects of it is adapted to him. The adolescent males doubted their ability to express themselves and to understand what would happen in the consultation, and therefore feared being dismissed without receiving any help. Such difficulties may be due to unfinished neurocognitive development and inexperience. They struggled with embarrassment, partly due to notions of masculinity, and strived to balance their needs of parental support, privacy, and being the one that the doctor listens to. Conclusions We argue that adolescent males are particularly vulnerable due to on-going neurocognitive and emotional development, inexperience, and notions of masculinity. However, good experiences can be generated through rather simple means. Adolescent males need individual adaptations demonstrating that they are cared for, understood and taken seriously. Furthermore, they need an unhurried pace to facilitate understanding, verbal affirmations to mitigate embarrassment, and help in navigating parental involvement.

Abstract Background Accurate diagnosis of axillary lymph node (ALN) metastases is essential for prognosis and treatment planning in breast cancer. Evaluation of ALN is done by ultrasound, which is limited by inter-operator variability, and by sentinel lymph node biopsy and/or ALN dissection, none of which are without risks and/or long-term complications. It is known that conventional 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limited sensitivity for ALN metastases. However, a recently developed dynamic whole-body (D-WB) [18F]FDG PET/CT scanning protocol, allowing for imaging of tissue [18F]FDG metabolic rate (MRFDG), has been shown to have the potential to increase lesion detectability. The study purpose was to examine detectability of malignant lesions in D-WB [18F]FDG PET/CT compared to conventional [18F]FDG PET/CT. Results This study prospectively included ten women with locally advanced breast cancer who were referred for an [18F]FDG PET/CT as part of their diagnostic work-up. They all underwent D-WB [18F]FDG PET/CT, consisting of a 6 min single bed dynamic scan over the chest region started at the time of tracer injection, a 64 min dynamic WB PET scan consisting of 16 continuous bed motion passes, and finally a contrast-enhanced CT scan, with generation of MRFDG parametric images. Lesion visibility was assessed by tumor-to-background and contrast-to-noise ratios using volumes of interest isocontouring tumors with a set limit of 50% of SUVmax and background volumes placed in the vicinity of tumors. Lesion visibility was best in the MRFDG images, with target-to-background values 2.28 (95% CI: 2.04–2.54) times higher than target-to-background values in SUV images, and contrast-to-noise values 1.23 (95% CI: 1.12–1.35) times higher than contrast-to-noise values in SUV images. Furthermore, five imaging experts visually assessed the images and three additional suspicious lesions were found in the MRFDG images compared to SUV images; one suspicious ALN, one suspicious parasternal lymph node, and one suspicious lesion located in the pelvic bone. Conclusions D-WB [18F]FDG PET/CT with MRFDG images show potential for improved lesion detectability compared to conventional SUV images in locally advanced breast cancer. Further validation in larger cohorts is needed. Clinical trial registration The trial is registered in clinicaltrials.gov, NCT05110443, https://www.clinicaltrials.gov/study/NCT05110443?term=NCT05110443&rank=1 .

Abstract Background Correct classification of estrogen receptor (ER) status is essential for prognosis and treatment planning in patients with breast cancer (BC). Therefore, it is recommended to sample tumor tissue from an accessible metastasis. However, ER expression can show intra- and intertumoral heterogeneity. 16α-[18F]fluoroestradiol ([18F]FES) Positron Emission Tomography/Computed Tomography (PET/CT) allows noninvasive whole-body (WB) identification of ER distribution and is usually performed as a single static image 60 min after radiotracer injection. Using dynamic whole-body (D-WB) PET imaging, we examine [18F]FES kinetics and explore whether Patlak parametric images ( $${K}_{i}$$ K i ) are quantitative and improve lesion visibility. Results This prospective study included eight patients with metastatic ER-positive BC scanned using a D-WB PET acquisition protocol. The kinetics of [18F]FES were best characterized by the irreversible two-tissue compartment model in tumor lesions and in the majority of organ tissues. $${K}_{i}$$ K i values from Patlak parametric images correlated with $${K}_{i}$$ K i values from the full kinetic analysis, r2 = 0.77, and with the semiquantitative mean standardized uptake value (SUVmean), r2 = 0.91. Furthermore, parametric $${K}_{i}$$ K i images had the highest target-to-background ratio (TBR) in 162/164 metastatic lesions and the highest contrast-to-noise ratio (CNR) in 99/164 lesions compared to conventional SUV images. TBR was 2.45 (95% confidence interval (CI): 2.25–2.68) and CNR 1.17 (95% CI: 1.08–1.26) times higher in $${K}_{i}$$ K i images compared to SUV images. These quantitative differences were seen as reduced background activity in the $${K}_{i}$$ K i images. Conclusion [18F]FES uptake is best described by an irreversible two-tissue compartment model. D-WB [18F]FES PET/CT scans can be used for direct reconstruction of parametric $${K}_{i}$$ K i images, with superior lesion visibility and $${K}_{i}$$ K i values comparable to $${K}_{i}$$ K i values found from full kinetic analyses. This may aid correct ER classification and treatment decisions. Trial registration ClinicalTrials.gov: NCT04150731, https://clinicaltrials.gov/study/NCT04150731